Association between the surgical approach and prognosis of spontaneous supratentorial deep intracerebral hemorrhage

The association between surgical approach and prognosis in patients with spontaneous supratentorial deep intracerebral hemorrhage is unclear. We aimed to explore the association between surgical approach and prognosis in these patients. A retrospective cohort of 311 patients from 3 centers who were treated with surgery 24 h after ictus was recruited. The surgical procedure involved removing the intracerebral hematoma using an aspirator through either the cortical approach or Sylvian fissure approach, assisted by an endoscope or microscope. The primary outcome was the one-year modified Rankin scale (mRS) score. The association between the surgical approach and the one-year mRS score was explored by using ordinal logistic regression and binary logistic regression. Baseline characteristics were balanced by propensity score matching and inverse propensity score weighting. In the adjusted analysis, compared with the cortex approach group, the Sylvian fissure approach group had better one-year mRS scores when analyzed as an ordinal variable (3.00 [2.00–4.00] vs. 4.00 [3.00–5.00]; adjusted odds ratio, 3.15; 95% CI, 1.78–5.58; p < 0.001) and a dichotomous variable (74.14% vs. 49.01%; adjusted odds ratio, 6.61; 95% CI, 2.75–15.88; p < 0.001). Surgical approach was not significantly associated with rebleeding (p = 0.88) or three-month mortality (p = 0.81). In univariate analysis after propensity score matching, there were significant differences in one-year mRS score between the two groups (p < 0.001), and there were no significant differences in rebleeding (Fisher’s exact test, p > 0.999) or three-month mortality (Fisher's exact test, p > 0.999). Inverse probability weighted regression analysis showed better one-year mRS scores when analyzed as an ordinal variable (adjusted odds ratio, 3.03; 95% CI, 2.17–4.17; p < 0.001) and a dichotomous variable (adjusted odds ratio, 3.11; 95% CI, 2.16–4.77; p < 0.001) in the Sylvian fissure approach group; the surgical approach was not significantly associated with rebleeding (p = 0.50) or three-month mortality (p = 0.60). In the surgical treatment of patients with spontaneous supratentorial deep intracerebral hemorrhage, the Sylvian fissure approach may lead to a better functional outcome compared with the cortex approach. Future prospective studies are warranted to confirm this finding.


Patients
This multicenter retrospective cohort study was approved by the Ethics Committees of the participating centers (the Ethics Committee of Chongqing University Central Hospital, the Ethics Committee of Yongchuan Hospital of Chongqing Medical University, and the Ethics Committee of the Third Affiliated Hospital of Chongqing Medical University) and registered in the Chinese Clinical Trial Center (registration number: ChiCTR2300069932).All methods were performed in accordance with the relevant guidelines and regulations.Patients at 3 centers (Chongqing University Central Hospital, Yongchuan Hospital of Chongqing Medical University, and the Third Affiliated Hospital of Chongqing Medical University) were enrolled between January 2017 and December 2021.
Inclusion criteria: first-time spontaneous intracerebral hemorrhage; age ≥ 18 years; hematoma located deep supratentorial; hematoma volume ≥ 20 ml; microscope-assisted or endoscope-assisted craniotomy with small bone window; surgery performed within 24 h after ictus.Exclusion criteria: hemorrhage of specific causes (aneurysm, cerebrovascular malformation, tumor, trauma); the main hematoma located in the subcortex or thalamus; the hematoma expanded into the ventricle, causing ventricle cast or hydrocephalus; the hematoma expanded into the brain stem; one or both pupils dilated and a Glasgow coma scale (GCS) score < 8; GCS score ≤ 4; the ictus time is not clear; platelet count < 100 × 10 9 ; coagulation dysfunction (International Normalized Ratio > 1.4); severe hepatic insufficiency, renal insufficiency, cardiac insufficiency and pulmonary insufficiency before ictus; mRS score ≥ 3 before ictus; malignant tumor; craniectomy (patients who underwent craniectomy in the reoperation were not excluded); hematoma puncture surgery (stereotaxis, hard and soft channels); bilateral intracerebral hemorrhage.

Treatment protocol
The treatment protocol included surgical treatments (transfrontal endoscope-assisted surgery and transtemporal endoscope-assisted or microscope-assisted surgery), nonsurgical treatments (monitoring and controlling blood pressure, hemostasis, etc.), and the management of complications during hospitalization (such as pulmonary infection, gastrointestinal bleeding, etc.).Details are available in the Supplement.
In transfrontal endoscope-assisted surgery, a small bone flap was created through a straight incision along the midline of the forehead.The hematoma's location was determined using noncontrast computed tomography image, and the endoscopic sheath tube was inserted after transfrontal cortical puncture.The intracerebral hematoma was then removed with endoscopic assistance through an aspirator.Following hemostasis in the operative area, a drainage tube was inserted.The scalp was sutured after securing the bone flap.
In transtemporal endoscope-assisted or microscope-assisted surgery, a small bone flap was created through a straight incision in the projection of Sylvian fissure's body surface.Puncture or fistulization of the insular cortex followed Sylvian fissure separation (or occurs directly in the cortex of the superior temporal gyrus).The intracerebral hematoma was then removed with an aspirator assisted by an endoscope or microscope.Following hemostasis in the operative area, a drainage tube was inserted.The scalp was sutured after securing the bone flap.

Imaging protocol
All patients underwent head noncontrast computed tomography (CT) examination on admission, and computed tomography angiography examination was completed on admission or before surgery to exclude aneurysms, arteriovenous malformations, etc.If the patient's arousal level before surgery was worse than that on admission, the head noncontrast CT examination was reexamined before surgery.Postoperative head noncontrast CT examination was performed (within 1 day, 1-3 days, 3-7 days) during subsequent hospitalization according to the patient's condition or at an interval of 7-10 days.

Clinical assessments
The observational indexes included sex, age, smoking history, drinking history, underlying diseases (diabetes, hypertension), antiplatelet therapy, anticoagulant therapy, systolic blood pressure (SBP) on admission, diastolic blood pressure (DBP) on admission, preoperative arousal level, preoperative GCS score, time of ictus, start time of surgery, surgical method (microscope-assisted or endoscope-assisted), surgical approach (cortex or Sylvian fissure), hematoma location (left or right), preoperative hematoma volume, preoperative midline shift, preoperative intraventricular hematoma, postoperative residual hematoma, postoperative rebleeding, postoperative reoperation and surgical methods.Patients were divided into the cortex approach (temporal cortex or frontal cortex) (control group) and the Sylvian fissure approach (treatment group).The primary outcome was mRS score at the one-year follow-up (one-year mRS score).The secondary outcomes were postoperative rebleeding (rebleeding) and mortality at the three-month follow-up (three-month mortality).The minimum follow-up period was 1 month, the maximum follow-up period was 12 months, and the median follow-up period was 12 months (95% confidence interval [CI]: 11.98-12.02).Patients were followed up via telephone or in outpatient clinics.The follow-up measurement was the mRS score.

Definitions and measurements
We defined supratentorial deep intracerebral hemorrhage and surgical timing.Additionally, we described the assessment methods for pertinent indicators, including arousal level, GCS score, mRS score, hematoma volume, midline shift, the presence or absence of postoperative residual hematoma/rebleeding in the operation area, and the indications for reoperation after the first surgery.Details are available in the Supplement.

Statistical analysis
We first evaluated the association among the clinical features, imaging features and outcomes by using a univariate analysis and the association between the surgical approach and outcomes by using an adjusted analysis.The baseline characteristics were balanced by propensity score matching and inverse probability weighting with propensity scores.Finally, the results were verified by propensity score adjustment analysis.Unordered categorical variables were expressed as counts and percentages.Ordinal categorical variables and continuous variables were expressed as medians (interquartile range [IQR]).
Univariate analyses included the chi-square test, Fisher's exact test, Mann-Whitney U test and Kruskal-Wallis test.In addition to the surgical approach, the independent variables with a p value < 0.05 in the univariate analysis were included in the multivariate logistic regression and multivariate ordinal logistic regression adjusted analysis, and the independent variables were verified by the variance inflation factor (VIF) to have no collinearity.The ordinal logistic regression model passed the test of parallel lines.1-year mRS score was analyzed as an ordinal variable and a dichotomous variable.

Propensity score
Univariate analysis was performed on the clinical and imaging features of the two groups of patients to determine the matching variables.The two groups were propensity score matched 1:1.The nearest neighbor matching method was used, and the caliper value was 0.2 of the standard deviation of the propensity score.The matching effect was evaluated by standard mean difference (SMD).After propensity score matching, the chi-square test and Mann-Whitney U test were used to compare the outcomes between the two groups.The association between surgical approach and outcomes was evaluated by logistic regression after inverse probability weighting with propensity scores.

Sensitivity analysis
In the multivariate logistic regression model, the robustness of the results was assessed by propensity score adjustment analysis.SPSS version 25.0 (IBM) and R version 4.2.2 (R Foundation for Statistical Computing) were used for statistical analysis.Propensity score matching was performed using the MatchIt package (version 4.5.0).All tests were two-sided, and a P value < 0.05 was considered statistically significant.

Ethical approval
Our institutional review boards (the Ethics Committee of Chongqing University Central Hospital, the Ethics Committee of Yongchuan Hospital of Chongqing Medical University, and the Ethics Committee of the Third Affiliated Hospital of Chongqing Medical University) approved this retrospective study and waived the requirement for informed consent from the patients.

Discussion
In the adjusted analysis, compared with the cortex approach group, the Sylvian fissure approach group had better one-year mRS scores as an ordinal variable (3.00 [2.00-4.00] vs. 4.00 [3.00-5.00];adjusted odds ratio, 3.15; 95% CI, 1.78-5.58;p < 0.001) and as a dichotomous variable (74.14% vs. 49.01%;adjusted odds ratio, 6.61; 95% CI, 2.75-15.88;p < 0.001).Surgical approach was not significantly associated with rebleeding (p = 0.88) or three-month mortality (p = 0.81).In univariate analysis after propensity score matching, there were significant differences in one-year mRS score between the two groups (p < 0.001), and there were no significant differences in rebleeding (Fisher's exact test, P > 0.999) or three-month mortality (Fisher's exact test, P > 0.999).Inverse probability weighted regression analysis showed better one-year mRS score as an ordinal variable (adjusted odds ratio, 3.03; 95% CI, 2.17-4.17;p < 0.001) and as a dichotomous variable (adjusted odds ratio, 3.11; 95% CI, 2.16-4.77;p < 0.001) in the Sylvian fissure approach group; the surgical approach was not significantly associated with rebleeding (p = 0.50) or three-month mortality (p = 0.60).Sensitivity analyses were consistent with the above results.The Sylvian fissure approach for the evacuation of supratentorial deep intracerebral hemorrhage was first proposed by Suzuki 19 in 1972, but it requires skilled dissection techniques of the vessels in the Sylvian fissure, which limits the options for less experienced surgeons 20 .Previous studies on the evacuation of spontaneous intracerebral hemorrhage through the Sylvian fissure approach are mainly case reports with small samples and short-term follow-up [21][22][23][24] , and the association between the Sylvian fissure approach and the prognosis of patients with spontaneous intracerebral hemorrhage is controversial.A total of 33 patients with spontaneous intracerebral hemorrhage were reported in the literature 25 , including 14 (44.42%)patients who underwent the Sylvian fissure approach and 19 (55.58%) patients who underwent the cortex approach.All patients had a hematoma volume ≥ 60 ml.There were no significant differences in 30-day mortality (14.29% vs. 31.58%)or Glasgow Outcome Scale (GOS) score ≥ 4 (35.71% vs. 31.58%)between the two groups.The large hematoma volume and short follow-up time of the patients included in this study may not fully reflect the advantages of the Sylvian fissure approach.A total of 66 patients with spontaneous intracerebral hemorrhage were reviewed 26 ; 47 (71.2%) were treated with surgery through the Sylvian fissure approach, and 19 (28.8%) were treated with medication.The hematoma volume was ≥ 30 ml in both groups.The two groups differed significantly in mortality (34.0% vs. 63.1%) and moderate disability (6-month GOS score = 4) (27.7% vs. 5.3%).Another study 27 reviewed 80 patients with spontaneous intracerebral hemorrhage, including 45 (56.25%) patients treated with the Sylvian fissure approach and 35 (43.75%) patients treated with the cortex approach.There was a significant  difference in functional outcome (Activities of Daily Living (ADL) score ≤ 3) at 6 months after surgery between the two groups (75% vs. 50%).A meta-analysis 28 included 659 patients from 7 studies, of which 329 (49.92%) patients were treated with the Sylvian fissure approach and 330 (50.08%) patients were treated with the cortex approach.The Sylvian fissure approach group had a higher hematoma clearance rate (odds ratio = 2.361, 95% CI: 1.443-3.861)and better postoperative functional outcome (GOS score ≥ 4 or ADL score ≤ 3) (odds ratio = 2.248, 95% CI: 1.498-3.160).
The results of this study suggest that compared with the cortex approach, the Sylvian fissure approach can obtain better one-year mRS scores without increasing the rate of postoperative rebleeding.The Sylvian fissure approach can avoid damaging the important functional cortex by cutting the insular cortex, especially in patients with dominant hemisphere hemorrhage [29][30][31] .The natural gap provided by the Sylvian fissure approach reduces the distance from the cortex to the hematoma 32 ; during the operation, with the release of cerebrospinal fluid and the evacuation of the hematoma, the Sylvian fissure provides sufficient traction space, thereby reducing additional damage to the cortex and deep white matter fibers such as the internal capsule.These advantages of the Sylvian fissure approach may lay the foundation for a better functional outcome for patients.In a recent retrospective cohort study 33 involving 134 consecutive patients with supratentorial intracerebral hemorrhage who underwent surgery, 66 patients underwent endoscopic hematoma evacuation under local anesthesia, while 68 patients underwent craniotomy hematoma evacuation under general anesthesia.Following the surgical concept proposed by the authors, where intentional retention of the hematoma was advocated to prevent additional damage to the brain, it was observed that the group undergoing endoscopic surgery under local anesthesia achieved better 6-month mRS scores.This study introduces a novel concept and foundation for surgery aimed at improving the prognosis of patients with supratentorial intracerebral hemorrhage.The integration of these concepts in the Sylvian fissure approach represents a promising avenue for further exploration to enhance the prognosis of patients with spontaneous supratentorial deep intracerebral hemorrhage.

Limitations
This study has some limitations.First, in the sensitivity analysis, multivariate ordinal logistic regression analysis with propensity score adjustment was not performed because the parallel line test failed, which may have led to biased results.Second, the outcome assessment was not blinded and was performed at times by a member of the surgical team, although this was consistent throughout the study period.Third, because the study lacked randomization, unmeasured confounders may be present.Fourth, only a few patients took antiplatelets and no patients took anticoagulants in this study, so the applicability of the results to such patients is poor.Fifth, among the 327 patients who met the inclusion and exclusion criteria, 16 patients (4.89%) had missing values due to loss of follow-up and were subsequently excluded.Although the proportion of excluded patients was small, the potential for selection bias cannot be completely ruled out.

Conclusions
In the surgical treatment of patients with spontaneous supratentorial deep intracerebral hemorrhage, the Sylvian fissure approach may provide better functional outcomes than the cortex approach.The results of this study provide a basis for improving the surgical efficacy for patients with spontaneous supratentorial deep intracerebral hemorrhage.Future prospective studies are warranted to confirm this finding.

Figure 1 .
Figure 1.Distribution of one-year modified Rankin scale (mRS) score (ordinal variable) according to type of surgical approach in the propensity score-matched cohort.The scores in the two groups were significantly different (Mann-Whitney U test [Z = − 3.83, p < 0.001]).The modified Rankin scale score ranges from 1 to 6, with higher scores indicating worse outcomes.

Table 3 .
Multivariable logistic regression of one-year mRS score (dichotomous variable).The Sylvian fissure approach was the treatment group a , and the cortex approach was the control group b .mRS, modified Rankin scale; CI, confidence interval; VIF, variance inflation factor; DBP, diastolic blood pressure; GCS, Glasgow Coma Scale.a Good one-year mRS score (74.14%).b Good one-year mRS score (49.01%).